The present invention is directed to biological valvular prosthesis and to methods of making the same. In particular, the present invention is directed to valvular prostheses formed from chemically fixed biological venous valve segments. These valvular prostheses contain one or more venous valves, with each venous valve having two or more leaflets chemically fixed in a position to ensure that the leaflets open under minimal forward blood flow pressures, but close under the application of backflow pressure.
There are different embodiments of the biological valvular prosthesis of the invention, each of which has a different type of application. Generally, the biological valvular prostheses are useful in applications which require the replacement of a valve. For example, one application involves the replacement of a defective or diseased venous valve. In another application the valvular prosthesis is used for correcting truncus arteriosus, a congenital defect where the pulmonary and aortic arteries join to form a single artery having a single valve. In this application the pulmonary and aortic arteries are surgically separated to isolate the blood flow. The valvular prosthesis of the invention is used to route blood from the right ventricle to the pulmonary artery. The integral valve of the valvular prosthesis functions as the semilunar valve normally present at the base of the pulmonary artery.
As stated, one application is the replacement of diseased or damaged venous valves. Venous valves are valves located in the veins. Blood circulated from the arterial to the venous system, with the blood pressure greatest in the arterial system. Blood pressure, as provided by heart activity in the arteries, is normally sufficient to maintain the flow of blood in one direction. The pressure of the blood in the veins is much lower than in the arteries principally due to the distance from the heart. The primary benefit of venous valves is the ability to limit backflow of blood traveling through the venous system. Numerous venous valves are located throughout the veins ensuring that the blood travels through the veins towards the heart.
The normally low blood pressure in the venous system is supplemented by the contraction of skeletal muscles. The contraction of the muscles compresses and drives the blood through the veins. The venous valves check blood flow through the veins, ensuring the drive of the blood towards the heart. Any damage to the venous valves disrupts this normal blood flow.
Venous valves also evenly distribute blood in the veins by segregating portions of blood flowing through the venous system. A further benefit provided by venous valves is checking the backflow of blood through the veins which minimizes or reduces the effect of a sudden increase in blood pressure, e.g. upon heavy exertion.
Venous valves are particularly important in the lower extremities, e.g. legs. The venous system in the lower extremities generally consists of deep veins and superficial veins which lie just below the skin surface. The deep and superficial veins are interconnected by perforating veins. Blood generally flows upwards through the legs towards the heart, and from the superficial to deep veins. The venous valves are situated in the deep, superficial and perforating veins to ensure the direction of blood flow.
Venous valves can become incompetent or damaged by disease, e.g. phlebitis, injury or a result of inherited malformation. Incompetent or damaged valves usually leak blood, even at low blood pressures. These valves fail to prevent the backflow of blood, which is particularly troublesome in the veins of the lower extremities.
The backflow of blood passing through leaking venous valves can cause numerous problems. As previously mentioned, blood normally flows upwards from the lower extremities, and from the superficial to deep veins. Leaking venous valves allow for blood regurgitation reflux causing blood to improperly flow back down through the veins. Blood can then stagnate in sections of certain veins, and in particular the veins in the lower extremities. This stagnation of blood raises blood pressure and dilates the veins and venous valves. The dilation of one vein may disrupt the proper functioning of other venous valves. The dilation of these valves may lead to chronic venous insufficiency. Chronic venous valve insufficiency may lead to skin pigmentation, edema and ulcers. If neglected, chronic valve insufficiency will require bed rest and eventually limb amputation.
Numerous therapies have been suggested to correct incompetent valves. Less invasive procedures include the use of elastic stockings. These procedures are usually inadequate for most conditions. Other procedures involve surgical operations to repair, reconstruct or replace the incompetent or damaged valves. Some investigators have attempted to repair incompetent valves by surgically restricting the valve circumference, such as by suturing the vein to form a tighter closing or restrict dilation of the valve. Other investigators attempted to restrict dilation of the valve by wrapping a stiff cloth about the valve.
Still other surgical procedures include valvuloplasty, transplantation and transposition of veins. Valvuloplasty involves the surgical reconstruction of the valve. Transposition of veins involves surgically bypassing sections of veins possessing the incompetent or damaged valves with veins possessing viable valves. Transplantation involves surgically transplanting one or more of a patient's viable valves for the incompetent or damaged valve. For a more detailed discussion of these techniques see Venous Valves, by R. Gottlob and R. May, published by Springer-Verlang/Wien, Part V, section 3. "Reconstruction of Venous Valves", 1986.
The above surgical procedures provide limited results. The leaflets of venous valves are generally thin, and once the valve becomes incompetent or destroyed, any repair provides only marginal relief. Venous valves are usually damaged during handling when the venous valve is being reconstructed, transpositioned or transplanted. The endothelium tissue layer of the vein may also be damaged during handling. This reduces the viability of the vein graft after implant.
Another disadvantage with transplantation procedures is the need to use the patient's own vein segment, otherwise the possibility of rejection arises. The use of a patient's own vein segment predisposes that the incompetence or damage did not arise from inherited factors or diseases which will affect the transplanted valve. For a complete discussion concerning the disadvantages of the discussed surgical procedures see the above referenced portion of "Venous Valves".
The only present alternative to the preceding surgical procedures is removing the valve completely. The removal of an incompetent valve at least prevents an impediment to normal blood flow. The problem associated with backflow is not overcome by the removal of the valve.
Many workers have sought to design a suitable valvular prosthesis. A prosthesis would have to provide a valve which would function similar to a natural valve.
A design of an artificial venous valve prosthesis was reported in "Development of a prosthetic venous valve", Schmidt et al, Journal of Biomedical Materials Research, Vol. 19, pages 827-832 (1985). These investigators attempted to prepare artificial venous valves. One type of artificial valve was constructed by molding glutaraldehyde fixed, umbilical cord segments. Specially treated segments were placed over the end of an aluminum rod which had been sculpted into a bicuspid shaped valve. Another type of artificial valve was prepared by dip casting a mandrel in liquid Pellethane polymer. The prepared casting was cut with a scalpel to define the separate valve leaflets. The results of the reported study indicate the necessity of constructing a more reliable artificial venous valve prosthesis.
In another investigation, researchers implanted cardiac prosthetic valves in canines, see "Venous Prosthetic Valves, The First Step Toward an Investigation in the Canine Model", Ami Gerlock M.D., Travis Phifer M.D. and John McDonald M.D., Investigative Radiology, Vol. (1986). The purpose of this investigation was to observe the operation of the larger, more rigid cardiac valve in the venous system. This study demonstrated the unsuitability of cardiac valvular prosthesis for transplantation in the venous system.
Xenograft monocusp patches were examined for possible use in repairing incompetent venous valves, see "Femoral Vein Valve Incompetence: Treatment with a Xenograft Monocusp Patch", Raul Garcia-Rinaldi, M.D., Ph.D., J. M. Revuelta, M.D., Ph.D., Manuel Martinez, M.D., Enrique Granda, M.D. and Luis De Santos, M.D., Journal of Vascular Surgery, Vol. 3, pages 932-935(1986). While these workers found some success in the implantation of patches, they recognized the advantage of a truly prosthetic device for replacement of incompetent venous valves.
A titanium venous valvular prosthesis has been suggested by Taheri. This valvular prosthesis is discussed more fully in "Experimental Prosthetic Vein Valve", Syde A. Taheri et al, "The American Journal of Surgery, Vol. 156, pages 111-114(1988). The major disadvantage with this type of prosthesis is hemolysis and thrombosis. Damage to the blood as it flows through the valve is enhanced by the small diameter of the valves. Use of such valves requires treatment of the patient with anticoagulants.
Prosthetic heart valves and vascular grafts are commercially available. Such devices may be constructed from artificial and natural materials. Natural tissues used for the construction of prosthetic devices are usually preserved, or fixed in a suitable chemical tanning procedure.
Chemical tanning procedures serve to preserve the tissue to minimize deterioration after implantation, and reduce the possibility of rejection of the device by the host. For example, natural tissues may be treated with a glutaraldehyde solution, with such processes taught in U.S. Pat. No. 4,372,743, issued to Lane on Feb. 8, 1983; and U.S. Pat. No. 3,966,401, issued to Hancock et al on Jun. 29, 1976.
The process taught in Lane involves a low pressure fixation process. This process reduces damage to the valve leaflets during the fixation process. The Hancock et al process involves the alternating pulsation of pressure within the heart valve or vessel.
Examples of prosthetic heart valves constructed at least partially from biological tissue are generally disclosed in U.S. Patent No. 3,736,598, issued to Bellhouse et al on Jun. 5, 1973; U.S. Pat. No. 2,832,078, issued to Williams on Apr. 29, 1958; U.S. Pat. No. 4,451,936, issued to Carpentier et al on Jun. 5, 1984; and U.S. Pat. No. 4,725,274, issued to Lane et al on Feb. 16, 1988.
Prosthetic vascular grafts are also known. Examples of vascular grafts or blood vessels prepared from artificial materials are disclosed in U.S. Patent Nos. 4,086,665, issued to Poirier on May 2, 1978; U.S. Pat. No 4,118,806, issued to Poirier on Oct. 10, 1978; and U.S. Pat. No. 4,670,286, issued to Nyilas et al on Jun. 2, 1987. The artificial blood vessels taught in the Poirier references may include porcine xenograft valves. The inclusion of the valve is required when the artificial blood vessel bypasses a natural heart valve. The main disadvantage with using the vascular graft containing a procine xenograft valve, as described in the Poirier references, is the development of luminal deposits of fibrinous material after a period of time. The development results from the synthetic grafts positioned on either side of the valve.
Vascular grafts may also be prepared from natural tissues. Such grafts are prepared by chemically treating segments of biografts. Examples of these grafts are disclosed in U.S. Pat. No. 4,671,797, issued to Vrandecic Pedero on Jun. 9, 1987 and U.S. Pat. No. 4,466,139, issued to Ketharanathan on Aug. 21, 1984. Hancock et al also discloses the preparation of veins and arteries.
While bioprosthetic heart valves and vascular grafts are known, bioprosthetic venous valves are presently not available. The major deterrent in constructing venous valves is the need to provide a valve which remains normally open, but closes under slight backflow. Another deterrent in constructing such valves is the need to provide proper valve leaflet and sinus geometry as the valve opens and closes. Prosthetic heart valves, and the methods of preparing the same, are not suitable as venous valve replacements. The unsuitability of using prosthetic cardiac valves as replacements for venous valves was discussed in the article by Gerlock et al. Prosthetic heart valves are usually made from porcine valves. Porcine heart valves have a geometry unsuitable as a replacement for venous valves. These types of valves are also generally larger than venous valves, and include valve leaflets generally thicker and stiffer than the leaflets of venous valves. The thicker heart valve leaflets require a greater opening pressure. The greater required opening pressure makes such valves unsuitable for the venous system.
The techniques used to prepare prosthetic heart valves make the resulting prosthesis more unsuitable for use as a venous valve replacement. As stated, venous valve leaflets are thinner and must remain open under normal venous flow conditions. The techniques used to prepare cardiac valvular prosthesis fix the leaflets to remain normally closed, and to open only upon the exertion of relatively higher pressures. These tanning techniques also form stiffer leaflets which further require greater pressures to open the valve.
This same rationale is also applicable to those procedures used for preparing vascular prothesis. The utilized tanning processes would not provide the valve leaflets with the ability to remain open during normal venous blood flow and close upon the occurrence of backflow. In fact, the patent to Vrandecic Pedero specifically requires the removal of any valves present in the arterial biograft used to prepare the vascular prosthesis.
It would thus remain desirable to provide a biological venous valvular prosthesis having leaflets which remain open under normal flow conditions, but close upon a minimal backflow.
A further application for the valvular prosthesis of the invention is in the treatment of congenital defects of the right ventricular outflow tract. For example, a valvular prosthesis in the form of a tubular member bearing at least one venous valve may be used to bypass a defective semilunar valve of the pulmonary artery, or even a defective pulmonary artery. Examples of defects of the right ventricular outflow tract are truncus arteriosus, pulmonary atresia and pulmonary stenosis.
Truncus arteriosus is a congenital cardiovascular malformation where a single artery, formed by the joining of the pulmonary and aortic arteries, arises from the heart. This single artery typically bridges the right and left ventricles. This congenital defect may al so be accompanied by a ventricular septal defect, which is a hole through the heart wall between the right and left ventricles.
While the mortality from this defect is high, attempts are usually made to repair the defect. This involves surgically separating the pulmonary segment from the aortic segment, and sealing the resulting opening of the aortic artery. If present, the ventricular septal defect is repaired by suturing the opening closed or suturing a patch over the opening. The pulmonary artery is then reconstructed by various techniques, which usually require the construction or insertion of a valve.
One technique utilizes a homograft which is surgically interposed in a graft sutured between the right ventricle and the pulmonary artery. For a more detailed discussion of this technique see "Truncus Arteriosus", Chapter 28 of CARDIAC SURGERY Morphology, Diagnostic Criteria, Natural History, Techniques, Results, and Indications, by John W. Kirklin, M.D. and Brian G. Barratt-Boyes, KBE, MB, ChM, Published by John Wiley & Sons (1986).
Another surgical procedure involves the construction of a bypass from the right ventricle to the pulmonary artery segment using a pericardial tissue patch. A pericardial monocusp is formed in the bypass. This procedure is discussed in more detail in "A technique for correction of truncus arteriosus types I and II without extracardiac conduits", by Barbero-Marcial M.D., Riso M.D., Atik M.D. and Jatene M.D., Journal of Thoracic and Cardiovascular Surgery, Vol. 99, Number 2, Feb. 1990.
A major disadvantage to the above discussed surgical procedures for the repair of truncus arteriosus is the use of multiple components in the reconstruction of the various arteries from the single large artery. That is, the first described procedure requires the use of a homograft and vascular graft, typically constructed from polytetrafluoroethylene, while the second procedure requires the use of a pericardial patch and a pericardial monocuspid. These procedures require extensive surgical implantation time, and provide sites for hemolysis.
While these discussed surgical procedures provide some relief from this debilitating congenital defect, improvements in the surgical techniques and prosthesis are necessary.